splice modulating agent. ABX464 is a first-in-class, small molecule inhibiting HIV replication through the inhibition of the Rev protein activity and modulation of RNA splicing. In collaboration with the team of Professor Jamal Tazi at the CNRS in Montpellier, France, Abivax designed ABX464 to lead to a clinically relevant improvement in HIV therapy. Preclinical data in humanized mice demonstrated that ABX464 monotherapy had an antiviral effect that was sustained following treatment interruption (Campos et al, Retrovirology 2015 12:30). A prior food-effect study demonstrated a three-fold increase in parent drug exposure when administered with food, without a significant impact on active glucuronide metabolite.

Disease: inflammatory bowel disease

Therapeutic
area: Inflammatory diseases - Gastrointestinal diseases

Country:

Trial
details:

Latest
news:

• On July 12, 2017, Abivax announced the publication of a paper on its lead product candidate ABX464 in the July 7, 2017 online edition ofNature Scientific Reports. The paper entitled “The Anti-HIV Candidate ABX464 Dampens Intestinal Inflammation by Triggering Il-22 Production in Activated Macrophages”, authored by Prof. Jamal Tazi, et al., summarizes the experiments that explored the mechanisms by which ABX464 exerts its anti-inflammatory properties, as well as implications for potential therapeutic use in inflammatory bowel disease.

The new publication summarizes the in vitro and in vivo findings with ABX464 on reducing inflammation, as well as potential therapeutic implications. ABX464 was shown to stimulate the expression of the anti-inflammatory cytokine IL-22 in macrophages in preclinical testing. In addition, ABX464 was shown to protect mice from the lethal effects of dextran sulfate sodium (“DSS”), which is an established animal model for experimental colitis. ABX464 treatment was not only critical for the survival of DSS-challenged mice, but also fully protected the histological structure of the murine intestine against changes induced by severe inflammation. RNA profiling analysis showed that ABX464 induced the expression of IL-22, and this was demonstrated both in DSS-challenged mice as well as in in vitro studies of LPS-stimulated bone marrow-derived macrophages. IL-22 is a cytokine that regulates tissue repair and recovery. The protective effect of ABX464 in these mice was substantially reduced by the simultaneous administration of antibodies to IL-22. ABX464 also showed a long-term protection against prolonged DSS-exposure after drug cessation. Furthermore, ABX464 reduced the colonic production of the pro-inflammatory cytokines IL-6 and TNFalpha and also the chemoattractant MCP-1. Abivax will now initiate a Phase 2a proof of concept clinical study in patients with ulcerative colitis during the second half of 2017.